The biological properties of immunoglobulin G and its split products [F(ab')2 and Fab]

Abstract

Antibodies of the IgG class possess antibacterial, antiviral and toxin neutralizing properties and for this reason are administered prophylactically and therapeutically. In the case of the immunoglobulin preparations commercially available for i.v. application a basic distinction must be made between unsplit immunoglobulins and those antibody preparations obtained by enzymatic digestion, such as F(ab')2 or Fab antibodies. This survey deals with the largely experimental evidence describing the biological properties of these preparations. Administration of antibodies in the presence of the corresponding antigens leads to the formation of immune complexes in the organism. These immune complexes can activate, either directly or indirectly, the cellular and humoral systems which are involved in phagocytosis and the elimination of antigens, in the regulation of the body's own antibody production and in inflammatory reactions. As a result of their inability to interact with Fc receptors, immune complexes with F(ab')2 or F(ab) antibodies appear to be less active in the release of inflammation mediators from leucocytes and thrombocytes than immune complexes with unsplit immunoglobulins. These, on the other hand, can antigen-specifically and non-antigen-specifically suppress the immune system which is not the case for immune complexes with F(ab')2 or Fab antibodies. There are indications that these split products also occur in vivo due to the action of tissue and leucocyte proteases. Unlike Fab preparations, F(ab')2 antibodies have antibacterial and antiviral potencies similar to unsplit immunoglobulins, which is probably due to the ability of F(ab')2 molecules to activate complement, not by the classical but by the alternative pathway. Like Fab preparations, F(ab')2 molecules appear to be superior to unsplit IgG in the elimination of haptens. On account of the relatively long period of time unsplit immunoglobulins remain in the blood, they are well suited for prophylactic treatment and substitution over longer periods. The extent to which indications, obtained predominantly from experimental studies, of a reduced release of inflammation mediators, a lack of immune suppression and a lack of augmentation of IgG catabolism would advocate the use of F(ab')2 split products, especially for therapeutic purposes, can only be ascertained after prospective and comparative studies have been carried out.

Efficacy and specificity of monoclonal antibodies to progesterone in preventing the establishment of pregnancy in the mouse

“…The anti¬ body is rapidly absorbed from the peritoneal cavity after injection and then slowly cleared from circu¬ lation with a t\ of about 80 h, a value similar to that reported previously (Spiegelberg & Weigle, 1965). F(ab')2 molecules which are metabolized more rapidly and do not interact with Fc receptors (Sedlacek, Gronski, Hofstaetter et al 1983) have a slight reduc¬ tion in the pregnancy rate. The F(ab')2 molecule had binding characteristics similar to the undigested molecule, so that its lower anti-implantation efficacy compared with that of intact DB3 was probably due to its increased rate of clearance from circulation (Morell & Stvaril, 1980;Burchiel, Burke, Breslow et al 1982).…”

Beneficial Immunomodulation by Streptococcus mutans Anti-P1 Monoclonal Antibodies Is Fc Independent and Correlates with Increased Exposure of a Relevant Target Epitope

“…All three of their cognate epitopes require an interaction of the discontinuous A- and P-regions of P1, with pre-A-region sequence contributing to the epitopes of 6-11A, 5-5D and 3-10E and post-P-region sequence also contributing to the epitope recognized by 3-10E (35–38). MAb 4-10A is similar to these MAbs in its requirement for the A-region-P-region interaction; however, it had previously been found to be neutral in its ability to promote the desirable bacterial adherence inhibiting response (34, 45). Because prozone-like effects of exogenously administered antibodies have been observed in ours and other systems and desirable results may require lower rather than higher amounts of antibody (23, 34, 46), 4-10A was re-evaluated in murine immunization experiments over a broader concentration range within the IC.…”

A mycobacterial lipoarabinomannan specific monoclonal antibody and its F(ab′)2 fragment prolong survival of mice infected withMycobacterium tuberculosis

“…Also, mice given F(ab′) 2 fragment of MoAb SMITB14 survived longer than mice given control F(ab′) 2 fragment. Protection afforded by the F(ab′) 2 fragments indicates lack of involvement of the Fc phagocytic receptor [31]. It can also be speculated that anti‐LAM antibodies and their F(ab′) 2 fragments, by binding to LAM, could interfere with LAM‐mediated inhibition of phagosome‐lysosome fusion [32].…”